Delving into the Latest Updates on TMX-202 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

TLR7

Mechanism

TLR7 agonists(Toll like receptor 7 agonists)

Therapeutic Areas

NeoplasmsInfectious DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication

Bladder CancerCondylomata AcuminataSkin Neoplasms

Inactive Indication-

Originator Organization

University of California San Diego

Active Organization

Telormedix SA

University of California San Diego

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC45H73N6O12P

InChIKeyDFFGHPOFYMBXJP-DIPNUNPCSA-N

CAS Registry1346110-99-3

Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0.1%, TMX-202 0.38%, vehicle solution or NaCl. On day 12 the rats were sacrificed and the bladders were evaluated histopathologically.

RESULTS:

No signs of toxicity were seen. The number of tumor-positive rats was 11 of 14 (79%) in the vehicle control group and in the NaCl control group, versus 9 of 14 (64%) in the TMX-101-treated group, and 8 of 14 (57%) in the TMX-20-treated group. The difference between tumor-bearing rats in the treated and control groups was not significant (p = 0.12). Bladder weight was significantly lower for TMX-202-treated rats compared to vehicle (p = 0.005).

CONCLUSIONS:

TMX-101 and TMX-202 are TLR-7 agonists with antitumor activity. Treatment with TMX-101 and TMX-202 resulted in less tumor-bearing rats compared to vehicle or saline control groups, although not statistically significant. In this aggressive bladder cancer model, a lower number of tumor-positive rats after treatment with TLR-7 agonists indicates activity for the treatment of non-muscle invasive bladder cancer.

01 May 2018·Urologic oncologyQ3 · MEDICINE

Pharmacokinetics and pharmacodynamics of intravesical and intravenous TMX-101 and TMX-202 in a F344 rat model

Q3 · MEDICINE

Article

Author: Oosterwijk, Egbert ; Witjes, Johannes Alfred ; Hulsbergen-van de Kaa, Christina A ; Maj, Roberto ; Falke, Johannes

OBJECTIVES:

To evaluate and compare the pharmacokinetic and pharmacodynamic properties of 2 investigational Toll-like receptor 7 agonists, TMX-101, and TMX-202 after intravenous and intravesical administration in a rat model. TLR-7 agonists are successfully used as topical treatment for various (pre)malignant skin lesions and are now under investigation as intravesical therapy for non-muscle-invasive bladder cancer.

METHODS:

Rats received an intravesical instillation with TMX-101, TMX-202, or vehicle. Additionally 2 groups of rats received an intravenous injection with TMX-101 or TMX-202. Blood sampling was performed at different time points, including pre-exposure and postexposure to determine the plasma concentrations of study drugs for pharmacokinetic and pharmacodynamic analyses and to determine the plasma concentrations of cytokines (IL-2, IL-6, and TNF-α).

RESULTS:

We observed no signs of toxicity after intravesical or intravenous administration. There was a limited dose dependent systemic uptake of TMX-101 and TMX-202 after intravesical administration. The systemic uptake of TMX-202 after intravesical instillation was 25 times lower compared to TMX-101.

CONCLUSIONS:

This in vivo study confirms the safety of intravesical TMX-101 and TMX-202 administration, with TMX-202 showing lower systemic uptake. TMX-202 has a larger molecule-mass compared to TMX-101, and it may therefore have a favorable safety profile when treating patients with non-muscle-invasive bladder cancer intravesically.

27 May 2016·Journal of biomedical opticsQ3 · MEDICINE

In vivo/ex vivotargeting of Langerhans cells after topical application of the immune response modifier TMX-202: confocal Raman microscopy and histology analysis

Q3 · MEDICINE

ArticleOA

Author: Roberto May ; Heike Richter ; Sabine Schanzer ; Maxim E. Darvin ; Dov Tamarkin ; Gisela Thiede ; Juergen Lademann ; Daniel Hasche ; Frank Rösl ; Yohan Hazot ; Sabrina E. Vinzón ; Saul Mujica Ascencio

The increased ability of TMX-202 (derivative of imiquimod) to penetrate the intact stratum corneum (SC) and the follicular orifices of porcine ear skin was shown ex vivo using confocal Raman microscopy and laser scanning microscopy. Moreover, to assess whether TMX-202 is able to reach the immune cells, Langerhans cells extracted from pretreated human skin were investigated ex vivo using confocal Raman microscopy combined with multivariate statistical methods. Tracking the Raman peak of dimethyl sulfoxide centered at 690 cm(−1), the absorption of TMX-202 containing formulation by Langerhans cells was shown. To answer the question whether the TMX-202 active ingredient is able to reach Langerhans cells, the attraction of immune cells to TMX-202 containing formulation treated skin was measured in the in vivo rodent model Mastomys coucha. The results show that TMX-202 active ingredient is able to reach Langerhans cells after penetrating through the intact skin and subsequently attract immune cells. Both the intercellular/transcellular as well as the follicular pathways allow the penetration through the intact barrier of the SC.

100 Deals associated with TMX-202

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bladder Cancer	Phase 1	-	Telormedix SA	-
Bladder Cancer	Phase 1	-	University of California San Diego	-
Condylomata Acuminata	Phase 1	-	Telormedix SA	-
Condylomata Acuminata	Phase 1	-	University of California San Diego	-
Skin Neoplasms	Phase 1	-	Telormedix SA	-
Skin Neoplasms	Phase 1	-	University of California San Diego	-